Other common name(s): Coley's toxins, mixed bacterial vaccines (MBVs), Issel's fever therapy
Scientific/medical name(s): none
Use of Coley toxins is an early form of immunotherapy, a method of treatment in which a person receives substances designed to boost the immune system and help the body fight off diseases such as cancer. The use of Coley toxins as a cancer treatment involves injecting killed bacterial cultures (Streptococcus pyogenes and Serratia marcescens) directly into the tumor or bloodstream.
Modern forms of immunotherapy are based on a better understanding of the effects of the immune system on cancer and are likely to be more effective. Although some practitioners continue to recommend and give Coley toxins, this treatment fell out of use decades ago by most oncologists in favor of more modern treatments. To most mainstream oncologists, the value of Coley's research was as a foundation for much of modern cancer immunotherapy. Some clinical research has been done on this very early form of cancer immunotherapy, but the strength of evidence is limited by the small number of cases and the fact that most research was done in the early part of the 20th century, when research methods were less rigorous than they are now. Some studies found that Coley toxins improved survival for people with certain forms of cancer, while other studies did not find a significant benefit.
How is it promoted for use?
Supporters claim Coley toxins stimulate the immune system in people with cancer, which helps to fight off disease. Some supporters also believe that tumor cells are more sensitive to heat than normal cells and that the high fever caused by Coley toxins helps to rid the body of cancer.
What does it involve?
Coley toxins are injected directly into the tumor or into the bloodstream in increasing daily doses until a fairly constant state of fever is reached. Treatment is often continued for several months. Patients are monitored closely for side effects and to control fevers as they develop.
The original formula for Coley toxins is no longer used in the United States, although similar formulas are used in at least one clinic. Coley toxins are used in Central America, Germany, and China, but it is not clear whether they are using the original Coley toxins or a combination of Coley toxins and other bacteria.
What is the history behind it?
Coley toxins were first used in the 1890s by William B. Coley, MD, a bone surgeon at Memorial Hospital in New York City (now Memorial Sloan-Kettering Cancer Center). After his attempt to save a young woman from bone cancer failed, Dr. Coley began reviewing bone cancer cases. He noted that cancer patients in whom bacterial infections developed after surgery seemed to have better outcomes than those who did not. He believed the bacterial infection helped to stimulate the immune system, causing it to fight off cancer cells. At first, Coley injected live bacteria into cancer patients, but because of the danger of serious or even fatal infection with that approach, he began using bacteria that had been killed. His treatment was controversial, despite some reports of cancer regression with its use. Dr. Coley passed away in 1936.
Different formulas of Coley toxins were made by several drug companies in the United States in the first half of the twentieth century. They were used to treat patients with a variety of types of cancer up until the early 1950s, when other forms of cancer treatment became more widely used.
Dr. Coley's daughter, Helen Coley Nauts, published several papers documenting her father's results. She also founded the Cancer Research Institute in New York in 1953, which continues to study how immunology can help diagnose and treat cancer.
Combinations of Coley toxins and other strains of bacteria are still being used at the Waisbren Clinic in Milwaukee, although the clinic recommends that patients try conventional treatments first. Coley toxins or similar treatments are also used in clinics in several other countries. There does not appear to be any active clinical research at this time into the use of the original Coley toxin formula. At least one pharmaceutical company is studying the use of pieces of DNA that may have contributed to the effectiveness of Coley toxins.
Dr. Coley is credited with pioneering the field of cancer immunotherapy. Immunotherapy is sometimes used alone but is more commonly combined with standard cancer treatments or used after conventional treatment. At this time, immunotherapy has a relatively small role in treating people with the most common types of cancer. However, researchers are optimistic that more effective immunotherapies can be developed that will have a greater impact on the outlook for people with cancer.
What is the evidence?
Scientific evidence suggests Coley toxins or other mixed bacterial vaccines may have a role in treating cancer when combined with other treatments. Coley reported his results as case series, which was the way most research was done in the early twentieth century. This format limits the ability of modern researchers to evaluate his findings. A retrospective review by researchers at the former University of Texas Center for Alternative Medicine compared 128 patients treated with surgery and Coley toxins between 1890 and 1960 to 1,675 similar patients treated in 1983 with conventional methods. The review found that survival rates for Coley's patients were about the same as those treated with more modern conventional methods. The University of Texas researchers point out that the study was limited by small sample size, short duration, and selection bias. More research would be needed to determine what benefit, if any, this therapy might have for people with cancer.
Results of three randomized clinical trials of Coley toxins or mixed bacterial vaccines have been published or presented. A 1962 article reported that more than one of 4 patients treated with Coley toxin showed objective improvement, whereas none of the patients who received a control vaccine made from different bacteria did.
A randomized trial of patients with nodular lymphoma (now known as follicular lymphoma) was discussed at a 1983 conference. Of the patients who received Coley toxins and chemotherapy, 85% had a complete response, in which all signs of cancer disappeared. This was compared with a 44% complete response rate in the patients who did not receive Coley toxins. Nodular lymphoma is among the cancer types that respond well to modern immunotherapy with monoclonal antibodies, however, so the relevance of this study to modern oncology practice is uncertain. The study was never reported in full in a journal, which has led some researchers to wonder whether long-term follow-up confirmed this degree of benefit.
Results of a Chinese study of patients with advanced liver cancer (hepatocellular carcinoma) were published in 1991. The study reported a significant benefit for patients with liver cancer that was too advanced for surgery, but no significant benefit in those who had surgery. Dr. Coley's earlier reports noted greatest success with sarcomas and lymphomas, and he eventually stopped treating patients with carcinomas. Reasons for the discrepancy between the older results and this more recent study are not clear.
Although Coley toxins are often regarded as an historic key step to modern immunotherapy, much has been learned about the immune system since that time. Modern immunotherapy is likely to be of greater value, especially in treating certain cancers, such as lymphoma, renal cell (kidney) cancer, and melanoma. Several recent laboratory and animal studies have been done to find out how Coley toxins might have worked, why they seemed useful for some cancer types and not others, and how modern methods could be used to develop immunotherapies that are more consistently effective and less toxic. Some immunologists believe that Coley toxins stimulated production of IL-12, a substance that can activate the immune system to attack cancer cells. Laboratory and clinical studies of IL-12 are currently in progress.
Are there any possible problems or complications?
These substances may have not been thoroughly tested to find out how they interact with medicines, foods, or dietary supplements. Even though some reports of interactions and harmful effects may be published, full studies of interactions and effects are not often available. Because of these limitations, any information on ill effects and interactions below should be considered incomplete.
The killed bacteria in Coley toxins can produce fever and nausea. Less common side effects can include headache, back pain, chills, chest pain, and shock-like reactions. There may be a danger that Coley toxins could produce serious infections among patients with weakened immune systems.
Women who are pregnant or breastfeeding should not use these toxins. Relying on this type of treatment alone and avoiding or delaying conventional medical care for cancer may have serious health consequences.
More information from your American Cancer Society
The following information on complementary and alternative therapies may also be helpful to you. These materials may be found on our Web site (www.cancer.org) or ordered from our toll-free number (1-800-ACS-2345).
The ACS Operational Statement on Complementary and Alternative Methods of Cancer Management
Alternative Medicine: Expanding Medical Horizons. A Report to the National Institutes of Health on Alternative Medical Systems and Practices in the United States. Washington, DC: US Government Printing Office; 1994. NIH publication 94-066.
Hoption Cann SA, Van Netten JP, Van Netten C. Dr William Coley and tumour regression: A place in history or in the future? Postgrad Med J. 2003;79:672-680.
Johnston B. Clinical effects of Coley's Toxins. 1. Controlled study. 2. A seven-year study. Cancer Chemotherapy Reports 1962;21:19-68.
Kempin S, Cirrencione C, Myers J, et al. Combined modality therapy of advanced nodular lymphomas (NL): The role of nonspecific immunotherapy (MBV) as an important determinant of responses and survival. Proc Am Soc Clin Oncol 1983;24:56. Meeting abstract.
McCarthy EF. The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas. Iowa Orthop J. 2006;26:154-158.
Richardson MA, Ramirez T, Russell NC, Moye LA. Coley toxins immunotherapy: a retrospective review. Altern Ther Health Med. 1999;5:42-47.
Starnes CO. Coley's toxins in perspective. Nature.357. 1992;357(6373):11-12.
Tang ZY, Zhou HY, Zhao G, Chai LM, Zhou M, Lu JZ, et al. Preliminary result of mixed bacterial vaccine as adjuvant treatment of hepatocellular carcinoma. Med Oncol & Tumor Pharmacother 1991;8:23-28.
Tsung K, Norton JA. Lessons from Coley's Toxin. Surg Oncol. 2006 Jul;15(1):25-28
University of Texas M.D. Anderson Cancer Center. Coley toxins: Detailed scientific review. 2006. Accessed at: www.mdanderson.org/departments/cimer/display.cfm?id=35F66009-F06A-11D4-810200508B603A14&method=displayFull&pn=6EB86A59-EBD9-11D4-810100508B603A14 on June 11, 2008.
Note: This information may not cover all possible claims, uses, actions, precautions, side effects or interactions. It is not intended as medical advice, and should not be relied upon as a substitute for consultation with your doctor, who is familiar with your medical situation.
Last Revised: 11/01/2008